There are over 250,000 paraplegics in the United States today. Since regeneration of the human spinal cord is abortive, a basic understanding of the mechanisms of potential growth and regenerative capacity of the vertebrate spinal cord is essential for patient management and eventual elimination of this national health problem. The morphology of the injured mammalian spinal cord will be studied with electron and light microscopy. The inability of the mammalian central nervous system to regenerate axons or axonal sprouting across the site of spinal cord lesion appears to be due to the reaction of the neurons just proximal to the site of lesion. Following spinal cord injury, the deafferented neurons in this region undergo morphological alteration (varicosity formation on dendrites, etc.). The altered neurons are non-selectively reinnervated by regenerating axonal sprouts of uninjured axons as well as by limited regeneration of severed axons. Axonal regeneration is preceeded by the alterations in neuron morphology. Depression of the neuronal reaction to injury by puromycin results in the regeneration of nerve fibers into the site of lesion. The present studies will attempt to quantify the neuronal reaction to injury and investigate the influence of drugs on the induction of axonal growth through the site of lesion into the denervated spinal cord. In addition, studies will be carried out on lower vertebrates to assess the ability of the lower vertebrate central nervous system to functionally regenerate versus the inability of the mammalian central nervous system to functionally integrate neuronal connections.